Blunted thermogenesis may reflect a subtle metabolic defect in energy expenditure in obesity. The role of insulin resistance in this defect is known, but new findings provide a basis for examining skeletal muscle and non-insulin mediated thermogenesis. Muscle is a determinant of resting metabolism, and may also be a site for the thermic effect of food (TEF). Muscle fiber types differ in insulin sensitivity, beta-receptor density and perhaps also in thermogenic capacity: Type I or II muscle fiber predominance may thus impact on energy expenditure. Mechanisms for the interactions between exercise and thermogenesis remain unclear, but changes in exercised muscle may play a role in the altered thermic effect of food. The proposed studies will investigate: 1)the role of muscle in TEF; 2)non-insulin mediated pathways of thermogenesis, including insulin-independent glucose uptake and sympathetic activity, at rest, during, and post-exercise. Protocol 1 will compare metabolic rate and thermogenesis in 2 groups of 15 lean and 2 groups of 15 obese men with normal or borderline hypertension, matched for insulin sensitivity at each. level of fatness, to test the hypothesis that increased sympathetic drive in hypertension independently increases energy -expenditure. Protocol 2 will quantify in 10 lean and 10 obese men skeletal muscle thermogenesis in relation to the systemic TEF at rest and after exercise, by measurement of whole body and forearm oxygen uptake after one-arm exercise. Two protocols will study non-insulin mediated glucose uptake (NIMGU) and non-insulin related thermogenesis: 1)the thermic effects of fructose, which is insulin-independent, will be compared in 10 lean and 10 obese men at rest and after exercise, without and with beta-blockade, to quantify the insulin independent sympathetic component of thermogenesis (Protocol 3); and 2) glucose uptake during insulinopenia will be studied in lean and obese men at rest and post-exercise and the thermic effect of NIMGU will be determined (Protocol 4). Protocol 5 will compare glucoregulation in lean and obese men during exercise, when insulin is low and glucose utilization is high, to test the hypothesis that peripheral glucose utilization during exercise is similar in the 2 groups, but hepatic glucose metabolism differs. In Protocol 6 the contribution of the thermic effect of food (TEF) to total energy expenditure will be compared in lean and obese men by use of doubly labeled water and indirect calorimetry during sedentary and daily-exercise conditions.The lean and obese men will be matched on age, fat-free mass, and fitness. The data will be used to determine the independent effects of obesity and increased sympathetic drive in hypertension on energy expenditure, and to compare in lean and obese men: 1)muscle fiber type and regional muscle metabolism in relation to systemic energy metabolism; 2)the contribution of NIMGU to thermogenesis at rest and after exercise; 3)regulation of glucose utilization during exercise; and 4)the relationship of thermogenesis to total energy expenditure in obesity. Clearer understanding of metabolic defects in obesity, and the impact of exercise in improving these defects, may lead to improved strategies for treating obesity.